Journal of Clinical Medicine

11 pages, 418 KiB

Open AccessArticle

Genotype and Phenotype Analyses in Pediatric Patients with HNF1B Mutations

by Seon Hee Lim, Ji Hyun Kim, Kyoung Hee Han, Yo Han Ahn, Hee Gyung Kang, Il-Soo Ha and Hae Il Cheong

J. Clin. Med. 2020, 9(7), 2320; https://doi.org/10.3390/jcm9072320 - 21 Jul 2020

Cited by 19 | Viewed by 3440

Abstract

HNF1B mutations, one of the most common causes of congenital anomalies of the kidney and urinary tract, manifest as various renal and extrarenal phenotypes. We analyzed the genotype-phenotype correlations in 14 pediatric patients with HNF1B mutations. Genetic studies revealed total gene deletion in [...] Read more.

HNF1B mutations, one of the most common causes of congenital anomalies of the kidney and urinary tract, manifest as various renal and extrarenal phenotypes. We analyzed the genotype-phenotype correlations in 14 pediatric patients with HNF1B mutations. Genetic studies revealed total gene deletion in six patients (43%). All patients had bilateral renal abnormalities, primarily multiple renal cysts. Twelve patients exhibited progressive renal functional deterioration, and six of them progressed to kidney failure. The annual reduction in estimated glomerular filtration rate was−2.1 mL/min/1.73 m². Diabetes developed in five patients (36%), including one patient with new-onset diabetes after transplantation. Neurological deficits were noted in three patients (21%), one with total gene deletion and two with missense mutations. Pancreatic abnormalities were more frequent in patients with missense mutations than in patients with other types of mutations. Genotype showed no significant correlation with renal outcomes or other extrarenal manifestations. The HNF1B scores at the times of onset and genetic diagnosis were <8 in two patients and one patient, respectively. Diagnosis of HNF1B mutations is clinically difficult because of extreme phenotypic variability and incomplete penetrance. Furthermore, some phenotypes develop with age. Therefore, patient age should be taken into consideration to increase the diagnostic rate, because some phenotypes develop with age. Full article

(This article belongs to the Section Nephrology & Urology)

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20 pages, 3598 KiB

Open AccessReview

Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors

by Sophie Deguelte, Marine Perrier, Cheryne Hammoutene, Guillaume Cadiot and Reza Kianmanesh

J. Clin. Med. 2020, 9(7), 2319; https://doi.org/10.3390/jcm9072319 - 21 Jul 2020

Cited by 21 | Viewed by 6162

Abstract

Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to [...] Read more.

Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to advanced stage at diagnosis, or palliative intent. Surgeons must be informed about the specific surgical management of SI-NETs according to their hormonal secretion, their usual dissemination at the time of diagnosis and the need for bowel-preserving surgery to avoid short bowel syndrome. The aim of this paper is to review the surgical indications and techniques, and perioperative and postoperative management of SI-NETs. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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12 pages, 975 KiB

Open AccessReview

Management of Bleeding Events Associated with Antiplatelet Therapy: Evidence, Uncertainties and Pitfalls

by Anne Godier, Pierre Albaladejo and the French Working Group on Perioperative Haemostasis (GIHP) Group

J. Clin. Med. 2020, 9(7), 2318; https://doi.org/10.3390/jcm9072318 - 21 Jul 2020

Cited by 18 | Viewed by 8747

Abstract

Bleeding complications are common in patients treated with antiplatelet agents (APA), but their management relies on poor evidence. Therefore, practical guidelines and guidance documents are mainly based on expert opinion. The French Working Group on Perioperative Haemostasis provided proposals in 2018 to enhance [...] Read more.

Bleeding complications are common in patients treated with antiplatelet agents (APA), but their management relies on poor evidence. Therefore, practical guidelines and guidance documents are mainly based on expert opinion. The French Working Group on Perioperative Haemostasis provided proposals in 2018 to enhance clinical decisions regarding the management of APA-treated patients with a bleeding event. In light of these proposals, this review discusses the evidence and uncertainties of the management of patients with a bleeding event while on antiplatelet therapy. Platelet transfusion is the main option as an attempt to neutralise the effect of APA on primary haemostasis. Nevertheless, efficacy of platelet transfusion to mitigate clinical consequences of bleeding in patients treated with APA depends on the type of antiplatelet therapy, the time from the last intake, the mechanism (spontaneous versus traumatic) and site of bleeding and the criteria of efficacy (in vitro, in vivo). Specific antidotes for APA neutralisation are needed, especially for ticagrelor, but are not available yet. Despite the amount of information that platelet function tests are expected to give, little data support the clinical benefit of using such tests for the management of bleeding events in patients treated or potentially treated with APA. Full article

(This article belongs to the Special Issue Platelet Counting, Morphology Assessment and Functional Studies: Pitfalls, Uncertainties, Good Practice for Clinical Usefulness)

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11 pages, 822 KiB

Open AccessArticle

Inhaled Dry Powder Antibiotics in Patients with Non-Cystic Fibrosis Bronchiectasis: Efficacy and Safety in a Real-Life Study

by Miguel Ángel Martínez-García, Grace Oscullo, Esther Barreiro, Selene Cuenca, Angela Cervera, Alicia Padilla-Galo, David de la Rosa, Annie Navarro, Rosa Giron, Francisco Carbonero, Maria Castro Otero and Francisco Casas

J. Clin. Med. 2020, 9(7), 2317; https://doi.org/10.3390/jcm9072317 - 21 Jul 2020

Cited by 6 | Viewed by 4001

Abstract

Background: Nebulised antibiotics are habitually used in patients with bronchiectasis, but the use of dry powder inhaled antibiotics (DPIA) in these patients is extremely limited. This study seeks to analyse the efficacy and safety of DPIA in bronchiectasis patients. Material and methods: Multi-centre [...] Read more.

Background: Nebulised antibiotics are habitually used in patients with bronchiectasis, but the use of dry powder inhaled antibiotics (DPIA) in these patients is extremely limited. This study seeks to analyse the efficacy and safety of DPIA in bronchiectasis patients. Material and methods: Multi-centre study of historic cohorts. All the hospital centres in Spain were contacted in order to collect data on patients with a diagnosis of bronchiectasis who had taken at least one dose of DPIA. Its efficacy was analysed in clinical, functional and microbiological terms by comparing the year before and the year after the prescription of DPIA. Adverse effects and variables associated with these effects, or any need to withdraw the drug, were also analysed. Results: 164 patients from 33 Spanish centres were included; 86% and 14% of these were treated with dry powder colistin and tobramycin, respectively. Chronic bronchial infection by Pseudomonas aeruginosa was present in 86% of these patients, and DPIA significantly reduced the number of exacerbations, the quantity and purulence of sputum and the isolation of pathogenic microorganisms. The most common adverse effect was cough (40%), particularly in cases of Chronic Obstructive Pulmonary Disease (COPD) and a previous cough and in those patients who had difficulties in handling the device. These factors were associated with a higher level of withdrawal of the treatment. There were no serious adverse effects. Conclusions: Our study suggests that DPIA are clinically efficacious and safe for treating bronchiectasis patients. Cough was shown to be the most common side-effect and reason for withdrawal of the treatment. Full article

(This article belongs to the Special Issue Cystic and Non-Cystic, Fibrosis Bronchiectasis: Drifting from Molecular to Clinical Practice)

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15 pages, 2297 KiB

Open AccessFeature PaperReview

The Impact of the Extent of Surgery on the Long-Term Outcomes of Patients with Low-Risk Differentiated Non-Medullary Thyroid Cancer: A Systematic Meta-Analysis

by Andreea Bojoga, Anna Koot, Johannes Bonenkamp, Johannes de Wilt, Joanna IntHout, Peep Stalmeier, Rosella Hermens, Johannes Smit, Petronella Ottevanger and Romana Netea-Maier

J. Clin. Med. 2020, 9(7), 2316; https://doi.org/10.3390/jcm9072316 - 21 Jul 2020

Cited by 20 | Viewed by 3269

Abstract

Recently, the management of patients with low-risk differentiated non-medullary thyroid cancer (DTC), including papillary and follicular thyroid carcinoma subtypes, has been critically appraised, questioning whether these patients might be overtreated without a clear clinical benefit. The American Thyroid Association (ATA) guideline suggests that [...] Read more.

Recently, the management of patients with low-risk differentiated non-medullary thyroid cancer (DTC), including papillary and follicular thyroid carcinoma subtypes, has been critically appraised, questioning whether these patients might be overtreated without a clear clinical benefit. The American Thyroid Association (ATA) guideline suggests that thyroid lobectomy (TL) could be a safe alternative for total thyroidectomy (TT) in patients with DTC up to 4 cm limited to the thyroid, without metastases. We conducted a meta-analysis to assess the clinical outcomes in patients with low-risk DTC based on the extent of surgery. The risk ratio (RR) of recurrence rate, overall survival (OS), disease-free survival (DFS) and disease specific survival (DSS) were estimated. In total 16 studies with 175,430 patients met the inclusion criteria. Overall, low recurrence rates were observed for both TL and TT groups (7 vs. 7%, RR 1.10, 95% CI 0.61–1.96, I² = 72%), and no statistically significant differences for OS (TL 94.1 vs. TT 94.4%, RR 0.99, CI 0.99–1.00, I² = 53%), DFS (TL 87 vs. TT 91%, RR 0.96, CI 0.89–1.03, I² = 85%), and DSS (TL 97.2 vs. TT 95.4%, RR 1.01, CI 1.00–1.01, I² = 74%). The high degree of heterogeneity of the studies is a notable limitation. Conservative management and appropriate follow-up instead of bilateral surgery would be justifiable in selected patients. These findings highlight the importance of shared-decision making in the management of patients with small, low-risk DTC. Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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12 pages, 909 KiB

Open AccessArticle

The Plasmatic Aldosterone and C-Reactive Protein Levels, and the Severity of Covid-19: The Dyhor-19 Study

by Orianne Villard, David Morquin, Nicolas Molinari, Isabelle Raingeard, Nicolas Nagot, Jean-Paul Cristol, Boris Jung, Camille Roubille, Vincent Foulongne, Pierre Fesler, Sylvain Lamure, Patrice Taourel, Amadou Konate, Alexandre Thibault Jacques Maria, Alain Makinson, Ivan Bertchansky, Romaric Larcher, Kada Klouche, Vincent Le Moing, Eric Renard and Philippe Guilpain Show full author list Hide full author list

J. Clin. Med. 2020, 9(7), 2315; https://doi.org/10.3390/jcm9072315 - 21 Jul 2020

Cited by 33 | Viewed by 6191

Abstract

Background. The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. Since the RAAS can induce and modulate pro-inflammatory [...] Read more.

Background. The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. Since the RAAS can induce and modulate pro-inflammatory responses, it could play a key role in the pathophysiology of Covid-19. Thus, we aimed to determine the levels of plasma renin and aldosterone as indicators of RAAS activation in a series of consecutively admitted patients for Covid-19 in our clinic. Methods. Plasma renin and aldosterone levels were measured, among the miscellaneous investigations needed for Covid-19 management, early after admission in our clinic. Disease severity was assessed using a seven-category ordinal scale. Primary outcome of interest was the severity of patients’ clinical courses. Results. Forty-four patients were included. At inclusion, 12 patients had mild clinical status, 25 moderate clinical status and 7 severe clinical status. In univariate analyses, aldosterone and C-reactive protein (CRP) levels at inclusion were significantly higher in patients with severe clinical course as compared to those with mild or moderate course (p < 0.01 and p = 0.03, respectively). In multivariate analyses, only aldosterone and CRP levels remained positively associated with severity. We also observed a positive significant correlation between aldosterone and CRP levels among patients with an aldosterone level greater than 102.5 pmol/L. Conclusions. Both plasmatic aldosterone and CRP levels at inclusion are associated with the clinical course of Covid-19. Our findings may open new perspectives in the understanding of the possible role of RAAS for Covid-19 outcome. Full article

(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)

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11 pages, 2571 KiB

Open AccessArticle

Effects of Biofeedback Training on Esophageal Peristalsis in Amyotrophic Lateral Sclerosis Patients with Dysphagia

by Jerzy Tomik, Klaudia Sowula, Piotr Ceranowicz, Mateusz Dworak and Kamila Stolcman

J. Clin. Med. 2020, 9(7), 2314; https://doi.org/10.3390/jcm9072314 - 21 Jul 2020

Cited by 3 | Viewed by 2552

Abstract

Esophageal manometry (EM) could serve as an objective method for the detection of esophageal peristalsis in patients with amyotrophic lateral sclerosis (ALS). In this group of patients, biofeedback training (BT) using the EM procedure is a promising method for the rehabilitation of swallowing [...] Read more.

Esophageal manometry (EM) could serve as an objective method for the detection of esophageal peristalsis in patients with amyotrophic lateral sclerosis (ALS). In this group of patients, biofeedback training (BT) using the EM procedure is a promising method for the rehabilitation of swallowing function. A total of 20 ALS patients with clinical evidence of dysphagia and who met WFN criteria were recruited for this study. The standard transnasal EM with solid-state transducers was performed, and swallows with water and saliva were initiated in all subjects and repeated at 30-s intervals. The median upper esophageal contractile amplitude, duration, and velocity results during the wet and dry swallows were evaluated and compared in both the ALS and the control groups. In ALS patients, in contrast to the control, significant abnormalities in all EM parameters were recorded, which implies a specific pattern of esophageal peristalsis. Twelve months after BT, the body mass index (BMI) of ALS patients who underwent BT (ALSBT) was compared to the BMI of those who did not (ALS1)—compared to the ALS1 group, ALSBT patients showed a slightly smaller drop in BMI value. We presume that BT using EM can be a promising tool for the improvement of the swallowing mechanism in ALS patients. Full article

(This article belongs to the Special Issue Clinical and Translational Research on Amyotrophic Lateral Sclerosis (ALS))

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11 pages, 963 KiB

Open AccessArticle

Accuracy of Panoramic Radiograph for Diagnosing Periodontitis Comparing to Clinical Examination

by Vanessa Machado, Luís Proença, Mariana Morgado, José João Mendes and João Botelho

J. Clin. Med. 2020, 9(7), 2313; https://doi.org/10.3390/jcm9072313 - 21 Jul 2020

Cited by 22 | Viewed by 7062

Abstract

In this study, we explore the diagnostic accuracy of a Radiographic-based Periodontal Bone Loss (R-PBL) method as a screening tool for periodontitis, in the form of radiographic bone loss, under the 2018 case definition in comparison to the 2012 case definition. The analysis [...] Read more.

In this study, we explore the diagnostic accuracy of a Radiographic-based Periodontal Bone Loss (R-PBL) method as a screening tool for periodontitis, in the form of radiographic bone loss, under the 2018 case definition in comparison to the 2012 case definition. The analysis was based on 456 patients (253 females and 203 males), screened for periodontal status in the Study of Periodontal Health in Almada-Seixal (SoPHiAS) project and subjected to a panoramic dental X-ray. Patients were diagnosed for the presence of periodontitis following the 2018 and 2012 case definition. R-PBL classification was defined by alveolar bone loss and diagnosed as no periodontitis (≥80% remaining alveolar bone), mild to moderate periodontitis (66% to 79%), or severe periodontitis (<66%). We appraise the X-ray quality to look for the influence on the performance of R-PBL. Sensitivity, specificity, accuracy, and precision, through several indicators, were determined. Performance measurement was assessed through binary and multiclass Receiver operating characteristic/are under the curve (ROC/AUC) analyses. Our results show that the tested R-PBL method under the 2018 case definition is a reliable tool in periodontitis cases screening. This method does not replace clinical periodontal evaluation, but rather, it screens patients towards a definitive periodontitis diagnosis. These results will contribute to support the development of automated prediction systems towards periodontitis surveillance. Full article

(This article belongs to the Special Issue Advances in Clinical and Translational Research of Oral Surgery, Biomaterials, and Oral Disease Management)

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17 pages, 1583 KiB

Open AccessBrief Report

Chemokine Receptors CCR1 and CCR2 on Peripheral Blood Mononuclear Cells of Newly Diagnosed Patients with the CD38-Positive Chronic Lymphocytic Leukemia

by Irina Kholodnyuk, Alla Rivkina, Laura Hippe, Simons Svirskis, Svetlana Kozireva, Ildze Ventina, Irina Spaka, Marina Soloveichika, Jelena Pavlova, Modra Murovska and Sandra Lejniece

J. Clin. Med. 2020, 9(7), 2312; https://doi.org/10.3390/jcm9072312 - 21 Jul 2020

Cited by 2 | Viewed by 2723

Abstract

Chemokines and their receptors direct migration and infiltration of immune cells. CCR1 and CCR2 maintain sequence similarity and respond to a number of the same chemokines secreted in lymphoid organs. Expression of CD38 on leukemic cells has been associated with poor clinical outcomes [...] Read more.

Chemokines and their receptors direct migration and infiltration of immune cells. CCR1 and CCR2 maintain sequence similarity and respond to a number of the same chemokines secreted in lymphoid organs. Expression of CD38 on leukemic cells has been associated with poor clinical outcomes in patients with chronic lymphocytic leukemia (CLL) and is considered as the negative predictor of progression. In our study of newly diagnosed CLL patients, which included 39 CD38-positive and 22 CD38-negative patients, CCR1 and/or CCR2 were always detected, using flow cytometry, on the peripheral blood (PB) CD19⁺CD5⁺ lymphocytes in patients with >30% of the CD38⁺ CD19⁺CD5⁺ lymphocytes (n = 16). Spearman’s rank correlation analysis determined correlations between the frequency of the CCR1- and CCR2-expressing PB CD19⁺CD5⁺ lymphocytes and the frequency of the CD38-positive CD19⁺CD5⁺ lymphocytes (r_s = 0.50 and r_s = 0.38, respectively). No significant correlations were observed between ZAP70 mRNA expression levels in PB mononuclear cells and the frequency of the circulating CCR1⁺ or CCR2⁺ CD19⁺CD5⁺ lymphocytes. Further association studies are needed to verify prognostic relevance of the CCR1/CCR2 expression on leukemic cells in CLL patients at diagnosis. We suggest that CCR1/CCR2 signaling pathways could represent attractive targets for development of CLL anti-progression therapeutics. Full article

(This article belongs to the Special Issue Lymphoma：New Diagnosis and Current Treatment Strategies)

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12 pages, 1671 KiB

Open AccessArticle

A Retrospective Propensity Score Matched Analysis Reveals Superiority of Hypothermic Machine Perfusion over Static Cold Storage in Deceased Donor Kidney Transplantation

by Silvia Gasteiger, Valeria Berchtold, Claudia Bösmüller, Lucie Dostal, Hanno Ulmer, Christina Bogensperger, Thomas Resch, Michael Rudnicki, Hannes Neuwirt, Rupert Oberhuber, Benno Cardini, Stefan Scheidl, Gert Mayer, Dietmar Öfner, Annemarie Weissenbacher and Stefan Schneeberger

J. Clin. Med. 2020, 9(7), 2311; https://doi.org/10.3390/jcm9072311 - 21 Jul 2020

Cited by 10 | Viewed by 2933

Abstract

Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS [...] Read more.

Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants performed between 08/2015 and 12/2019 (n = 347) were propensity score (PS) matched for cold ischemia time (CIT), extended criteria donor (ECD), gender mismatch, cytomegalovirus (CMV) mismatch, re-transplantation and Eurotransplant (ET) senior program. A total of 103 HMP and 103 SCS instances fitted the matching criteria. Prior to PS matching, the CIT was longer in the HMP group (17.5 h vs. 13.3 h; p < 0.001), while the delayed graft function (DGF) rates were 29.8% and 32.3% in HMP and SCS, respectively. In the PS matched groups, the DGF rate was 64.1% in SCS vs. 31.1% following HMP: equivalent to a 51.5% reduction of the DGF rate (OR 0.485, 95% CI 0.318–0.740). DGF was associated with decreased 1- and 3-year graft survival (100% and 96.3% vs. 90.8% and 86.7%, p = 0.001 and p = 0.008) or a 4.1-fold increased risk of graft failure (HR = 4.108; 95% CI: 1.336–12.631; p = 0.014). HMP significantly reduces DGF in kidney transplantation. DGF remains a strong predictor of graft survival. Full article

(This article belongs to the Special Issue Prevention and Treatment of Acute Kidney Injury)

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16 pages, 2623 KiB

Open AccessArticle

Optimizing Preparative Regimen for Umbilical Cord Blood Transplantation in Adult Acute Leukemia Patients: Acute Lymphoblastic Leukemia Requires Myeloablative Conditioning but Not Acute Myeloid Leukemia

by Ja Min Byun, Junshik Hong, Doyeun Oh, Ho-Young Yhim, Young Rok Do, Joon Seong Park, Chul Won Jung, Deok-Hwan Yang, Jong-Ho Won, Hong Ghi Lee, Joon Ho Moon, Yeung-Chul Mun, Deog-Yeon Jo, Jae Joon Han, Je-Hwan Lee, Jae Hoon Lee, Junglim Lee and Sung-Soo Yoon

J. Clin. Med. 2020, 9(7), 2310; https://doi.org/10.3390/jcm9072310 - 21 Jul 2020

Cited by 1 | Viewed by 2575

Abstract

Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host [...] Read more.

Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) (p = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG (p = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC (p = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT. Full article

(This article belongs to the Special Issue Stem Cell Transplantation in Hematological Malignancies)

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27 pages, 3658 KiB

Open AccessReview

Inner Ear Gene Therapies Take Off: Current Promises and Future Challenges

by Sedigheh Delmaghani and Aziz El-Amraoui

J. Clin. Med. 2020, 9(7), 2309; https://doi.org/10.3390/jcm9072309 - 21 Jul 2020

Cited by 79 | Viewed by 12060

Abstract

Hearing impairment is the most frequent sensory deficit in humans of all age groups, from children (1/500) to the elderly (more than 50% of the over-75 s). Over 50% of congenital deafness are hereditary in nature. The other major causes of deafness, which [...] Read more.

Hearing impairment is the most frequent sensory deficit in humans of all age groups, from children (1/500) to the elderly (more than 50% of the over-75 s). Over 50% of congenital deafness are hereditary in nature. The other major causes of deafness, which also may have genetic predisposition, are aging, acoustic trauma, ototoxic drugs such as aminoglycosides, and noise exposure. Over the last two decades, the study of inherited deafness forms and related animal models has been instrumental in deciphering the molecular, cellular, and physiological mechanisms of disease. However, there is still no curative treatment for sensorineural deafness. Hearing loss is currently palliated by rehabilitation methods: conventional hearing aids, and for more severe forms, cochlear implants. Efforts are continuing to improve these devices to help users to understand speech in noisy environments and to appreciate music. However, neither approach can mediate a full recovery of hearing sensitivity and/or restoration of the native inner ear sensory epithelia. New therapeutic approaches based on gene transfer and gene editing tools are being developed in animal models. In this review, we focus on the successful restoration of auditory and vestibular functions in certain inner ear conditions, paving the way for future clinical applications. Full article

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

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15 pages, 2119 KiB

Open AccessArticle

Diagnostic Performance of [¹⁸F]Fluorocholine and [⁶⁸Ga]Ga-PSMA PET/CT in Prostate Cancer: A Comparative Study

by Zeinab Paymani, Taryn Rohringer, Reza Vali, Wolfgang Loidl, Nafiseh Alemohammad, Hans Geinitz, Werner Langsteger and Mohsen Beheshti

J. Clin. Med. 2020, 9(7), 2308; https://doi.org/10.3390/jcm9072308 - 21 Jul 2020

Cited by 12 | Viewed by 5308

Abstract

The current study endeavored to closely compare the detection rate of 68-Gallium labelled prostate-specific membrane antigen ([⁶⁸Ga]Ga-PSMA) versus [¹⁸F]Fluorocholine in men with prostate cancer (PC), to investigate the benefits and pitfalls of each modality in the setting of various [...] Read more.

The current study endeavored to closely compare the detection rate of 68-Gallium labelled prostate-specific membrane antigen ([⁶⁸Ga]Ga-PSMA) versus [¹⁸F]Fluorocholine in men with prostate cancer (PC), to investigate the benefits and pitfalls of each modality in the setting of various patient characteristics. We retrospectively analyzed 29 biopsy-proven PC patients in two categories, staging and restaging, who underwent both scans within a maximum of 30 days of each other. Variables including patient demographics, prostate specific antigen (PSA) level, Gleason score, clinical course, and following treatments were recorded. The number and location of suspicious lesions as well as uptake values were noted. A total of 148 suspicious lesions were detected, of which 70.9% (105/148) were concordantly visualized in both imaging modalities. [⁶⁸Ga]Ga-PSMA positron emission tomography/computed tomography (PET/CT) revealed a higher number of metastatic lesions per patients (91% vs 78%). The mean of maximum standardized uptake value (SUV max) in concordant lesions was significantly higher in [⁶⁸Ga]Ga-PSMA compared to [¹⁸F]Fluorocholine PET/CT (14.6 ± 8.44 vs. 6.9 ± 3.4, p = 0.001). Discordant lesions were detected by both modalities, but more frequently by [⁶⁸Ga]Ga-PSMA PET/CT (20.3% in [⁶⁸Ga]Ga-PSMA versus 8.8% by [¹⁸F]Fluorocholine PET/CT). In patients with PSA levels below 1.0 ng/mL and <2.0 ng/mL, [¹⁸F]Fluorocholine PET/CT detection rate was half (57% and 55%, respectively) that of [⁶⁸Ga]Ga-PSMA PET/CT. Tumor, nodes and metastases (TNM) staging, and subsequently patient management, was only influenced in 4/29 patients (14%), particularly by [⁶⁸Ga]Ga-PSMA PET/CT with PSA values under 0.5 ng/mL. [⁶⁸Ga]Ga-PSMA PET/CT revealed superior diagnostic performance to [¹⁸F]Fluorocholine PET/CT in staging and restaging of PC patients, especially in cases with low PSA levels. However, in a few hormone resistant high-risk PC patients, [¹⁸F]Fluorocholine PET/CT may improve overall diagnostic accuracy. Full article

(This article belongs to the Special Issue Emerging Technologies for Medical Imaging - Diagnostics, Monitoring and Therapy of Cancers)

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3 pages, 164 KiB

Open AccessEditorial

New Clue: Prediction from Cell-Free DNA

by Yan Y. Sanders

J. Clin. Med. 2020, 9(7), 2307; https://doi.org/10.3390/jcm9072307 - 21 Jul 2020

Cited by 4 | Viewed by 1937

Abstract

The main challenge for a positive long-term outcome in lung transplantation is the lack of early detection for chronic lung allograft dysfunction (CLAD). With advancements in technology, an increasing number of studies demonstrate that cell-free DNA (cfDNA) in body fluids could be used [...] Read more.

The main challenge for a positive long-term outcome in lung transplantation is the lack of early detection for chronic lung allograft dysfunction (CLAD). With advancements in technology, an increasing number of studies demonstrate that cell-free DNA (cfDNA) in body fluids could be used as a marker for disease diagnosis, prognosis or monitoring response to treatment. A previous report from this journal found the joint assessment of cfDNA and CXCL10 from brochoalveolar lavage (BAL) could determine the subphenotypes of CLAD and predict lung transplant survival. This is an exciting attempt in monitoring the progress for lung transplant recipients. More studies and better understanding of cfDNA are needed to develop an accessible and reliable biomarker to monitor the progress of CLAD to improve the long-term survival for lung transplant recipients. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

21 pages, 5043 KiB

Open AccessArticle

by Vilfredo De Pascalis, Giuliana Cirillo, Arianna Vecchio and Joseph Ciorciari

J. Clin. Med. 2020, 9(7), 2306; https://doi.org/10.3390/jcm9072306 - 21 Jul 2020

Cited by 6 | Viewed by 3423

Abstract

This study explored the electrocortical correlates of conscious and nonconscious perceptions of emotionally laden faces in neurotypical adult women with varying levels of autistic-like traits (Autism Spectrum Quotient—AQ). Event-related potentials (ERPs) were recorded during the viewing of backward-masked images for happy, neutral, and [...] Read more.

This study explored the electrocortical correlates of conscious and nonconscious perceptions of emotionally laden faces in neurotypical adult women with varying levels of autistic-like traits (Autism Spectrum Quotient—AQ). Event-related potentials (ERPs) were recorded during the viewing of backward-masked images for happy, neutral, and sad faces presented either below (16 ms—subliminal) or above the level of visual conscious awareness (167 ms—supraliminal). Sad compared to happy faces elicited larger frontal-central N1, N2, and occipital P3 waves. We observed larger N1 amplitudes to sad faces than to happy and neutral faces in High-AQ (but not Low-AQ) scorers. Additionally, High-AQ scorers had a relatively larger P3 at the occipital region to sad faces. Regardless of the AQ score, subliminal perceived emotional faces elicited shorter N1, N2, and P3 latencies than supraliminal faces. Happy and sad faces had shorter N170 latency in the supraliminal than subliminal condition. High-AQ participants had a longer N1 latency over the occipital region than Low-AQ ones. In Low-AQ individuals (but not in High-AQ ones), emotional recognition with female faces produced a longer N170 latency than with male faces. N4 latency was shorter to female faces than male faces. These findings are discussed in view of their clinical implications and extension to autism. Full article

(This article belongs to the Section Clinical Neurology)

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11 pages, 917 KiB

Open AccessArticle

Does ADHD Symptomatology Influence Treatment Outcome and Dropout Risk in Eating Disorders? A longitudinal Study

by Giulia Testa, Isabel Baenas, Cristina Vintró-Alcaraz, Roser Granero, Zaida Agüera, Isabel Sánchez, Nadine Riesco, Susana Jiménez-Murcia and Fernando Fernández-Aranda

J. Clin. Med. 2020, 9(7), 2305; https://doi.org/10.3390/jcm9072305 - 20 Jul 2020

Cited by 13 | Viewed by 4939

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and its symptoms have been shown to be present in patients with eating disorders (EDs) and are associated with increased psychopathology and more dysfunctional personality traits. This study aimed to assess if the presence of ADHD symptoms in patients with [...] Read more.

Attention-deficit/hyperactivity disorder (ADHD) and its symptoms have been shown to be present in patients with eating disorders (EDs) and are associated with increased psychopathology and more dysfunctional personality traits. This study aimed to assess if the presence of ADHD symptoms in patients with EDs affects their short and long-term therapy outcome. A total of 136 consecutively treated ED patients were considered in this study. Baseline pre-treatment evaluation included the Adult ADHD Self-Report Scale (ASRS v1.1) for ADHD symptoms and the assessment of eating symptomatology using the Eating Disorders Inventory (EDI-2). Treatment outcome was evaluated in terms of ED symptoms after cognitive behavioral therapy (CBT) and dropout rate during treatment. Furthermore, we evaluated ED symptoms in treatment completers after a follow-up of 8 years on average. Path analyses assessed the potential mediational role of the EDI-2 total score in the relationship between ADHD and treatment outcome. Results showed that baseline symptoms of ADHD indirectly affected treatment outcome after CBT; the ASRS positive screening was related to higher eating symptomatology (standardized coefficient B = 0.41, p = 0.001, 95% CI: 0.26 to 0.55), and the presence of high ED levels contributed to the increase of dropout (B = 0.15, p = 0.041, 95% CI: 0.03 to 0.33) and a worse treatment outcome (B = 0.18, p = 0.041, 95% CI: 0.01 to 0.35). No direct effect was found between the ASRS positive screening with the risk of dropout (B = −0.08, p = 0.375) and worse treatment outcome (B = −0.07, p = 0.414). These results suggest the relevance of identifying specific treatment approaches for patients with ADHD symptoms and severe eating symptomatology. Full article

(This article belongs to the Special Issue Advances in Eating Disorders)

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15 pages, 1326 KiB

Open AccessArticle

Sleep Impairment and Psychological Distress among Patients with Inflammatory Bowel Disease—beyond the Obvious

by Georgiana-Emmanuela Gîlc-Blanariu, Gabriela Ștefnescu, Anca Victorița Trifan, Mihaela Moscalu, Mihail-Gabriel Dimofte, Cristinel Ștefnescu, Vasile Liviu Drug, Vlad-Adrian Afrsnie and Manuela Ciocoiu

J. Clin. Med. 2020, 9(7), 2304; https://doi.org/10.3390/jcm9072304 - 20 Jul 2020

Cited by 21 | Viewed by 3705

Abstract

Background: A healthy sleep–wake cycle is fundamental for regulating immune function. Sleepiness and fatigue are often manifestations of chronic inflammatory disorders, such as inflammatory bowel disease (IBD), potentially influencing the course of the disease. Our aim was to characterize sleep impairment in patients [...] Read more.

Background: A healthy sleep–wake cycle is fundamental for regulating immune function. Sleepiness and fatigue are often manifestations of chronic inflammatory disorders, such as inflammatory bowel disease (IBD), potentially influencing the course of the disease. Our aim was to characterize sleep impairment in patients with IBD and to identify potential associated factors. Methods: We conducted a single-center prospective case control study including IBD patients and healthy controls. We evaluated clinical and biochemical parameters, sleep impairment through Pittsburgh Sleep Quality Index (PSQI) and anxiety and depression through Hospital Anxiety and Depression Scale (HADS) questionnaires. Results: In total, 110 patients with IBD and 66 healthy controls were included. Patients with IBD had a significantly altered sleep quality compared to the control group (p < 0.001), with sleep impairment also occurring for patients in remission (median PSQI = 7), but without significant differences between ulcerative colitis and Crohn’s disease. However, PSQI was correlated with disease activity scores only for ulcerative colitis and not for Crohn’s disease. Among patients with increased PSQI, only 30.19% used sleep medication. Sleep impairment was significantly correlated with altered psychological status (p < 0.01) and the presence of extraintestinal manifestations (p = 0.0172). Conclusions: Sleep impairment is frequent among patients with IBD, is associated with psychological distress and several disease-related parameters and should be routinely evaluated, at least in several IBD patient subgroups, to improve disease management. Full article

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

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12 pages, 532 KiB

Open AccessArticle

Predictive Value of Serial ECGs in Patients with Suspected Myocardial Infarction

by Jonas Lehmacher, Johannes Tobias Neumann, Nils Arne Sörensen, Alina Goßling, Paul Michael Haller, Tau Sarra Hartikainen, Peter Clemmensen, Tanja Zeller, Stefan Blankenberg and Dirk Westermann

J. Clin. Med. 2020, 9(7), 2303; https://doi.org/10.3390/jcm9072303 - 20 Jul 2020

Cited by 11 | Viewed by 4584

Abstract

The electrocardiogram (ECG) is an important diagnostic tool for patients with suspected acute myocardial infarction (AMI). Current guidelines recommend serial ECGs in case of persisting symptoms. We aimed to analyze the predictive value of ischemic ECG-signs in patients with suspected AMI. Patients presenting [...] Read more.

The electrocardiogram (ECG) is an important diagnostic tool for patients with suspected acute myocardial infarction (AMI). Current guidelines recommend serial ECGs in case of persisting symptoms. We aimed to analyze the predictive value of ischemic ECG-signs in patients with suspected AMI. Patients presenting to the emergency department with suspected AMI were included. All patients with ST-elevation AMI were excluded from analyses. Patients received 12-lead-ECG and high-sensitive Troponin T (hs-TnT)-measurement at admission and after 3 h. Four groups were defined: no ischemic signs in either ECG; new ischemic signs in the second ECG; resolved ischemic signs in the second ECG; and persistent ischemic signs in both ECGs. Patients were followed for 2 years to assess the composite endpoint of all-cause-mortality, AMI, and coronary revascularization. Using a 30-day landmark analysis, a Cox regression with ischemic signs as the variable of interest, adjusted by cardiovascular risk factors, was calculated. Of 1675 patients, 1321 showed no ischemic signs, in 25 new-, in 92 resolved- and in 237 patients, persistent ischemic signs were documented. Patients with persistent ischemic signs had significantly worse outcomes, compared to those without. Compared to no ischemic signs, adjusted hazard ratios for the combined endpoint were 0.81 (95% CI 0.20, 3.31; p-value = 0.77) for new-, 0.59 (95% CI 0.26, 1.34; p-value = 0.21) for resolved-, and 1.47 (95% CI 1.102, 2.13; p-value = 0.041) for persistent ischemic signs. In patients with suspected AMI, persistent ischemic ECG-signs are predictive of a higher rate of all-cause-mortality, AMI, and revascularization. Full article

(This article belongs to the Special Issue Myocardial Infarction and Myocardial Injury in Acute Cardiac Care)

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21 pages, 1970 KiB

Open AccessReview

The Role of Interventional Radiology for the Treatment of Hepatic Metastases from Neuroendocrine Tumor: An Updated Review

by Maxime Barat, Anne-Ségolène Cottereau, Alice Kedra, Solène Dermine, Lola-Jade Palmieri, Romain Coriat, Raphael Dautry, Lambros Tselikas, Philippe Soyer and Anthony Dohan

J. Clin. Med. 2020, 9(7), 2302; https://doi.org/10.3390/jcm9072302 - 20 Jul 2020

Cited by 29 | Viewed by 5350

Abstract

Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall [...] Read more.

Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall survival. These treatment options are proposed in patients with NELM not responding to systemic therapies and without extrahepatic progression. Currently, available data suggest that TAE should be preferred to TACE in patients with NELM from extrapancreatic origin because of similar efficacy and better patient tolerance. TACE is more effective in patients with pancreatic NELM and SIRT has shown promising results along with good tolerance. However, large randomized controlled trials are still lacking in this setting. Available literature mainly consists in small sample size and retrospective studies with important technical heterogeneity. The purpose of this review is to provide an updated overview of the currently reported endovascular interventional radiology procedures that are used for the treatment of NELM. Full article

(This article belongs to the Special Issue Neuroendocrine Tumors and Therapeutic Optimization)

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14 pages, 584 KiB

Open AccessArticle

Creating and Validating the DESEA Questionnaire for Men and Women

by Francisco Cabello-Santamaría, Marina A. Cabello-García, Jerónimo Aragón-Vela and F. Javier del Río

J. Clin. Med. 2020, 9(7), 2301; https://doi.org/10.3390/jcm9072301 - 20 Jul 2020

Cited by 6 | Viewed by 3519

Abstract

In clinical practice, it is essential to be able to identify hypoactive sexual desire disorder (HSDD), with its different severity levels and assess the influence the subject’s relationship has on the issue. In order to do this, questionnaires are needed that comprise appropriate [...] Read more.

In clinical practice, it is essential to be able to identify hypoactive sexual desire disorder (HSDD), with its different severity levels and assess the influence the subject’s relationship has on the issue. In order to do this, questionnaires are needed that comprise appropriate psychometric properties. We analyzed the psychometric properties and factorial structure of the Sexual Desire and Aversion (DESEA) questionnaire that evaluates sexual desire and interpersonal stress (relationship problems) in male and female couples. A pilot study was conducted with a group of 1583 people. Finally, it included 20,424 Spanish speakers who answered the questionnaire via an online link. The requirements for factor analysis were verified followed by the exploratory and confirmatory factor analysis. The Cronbach’s alpha coefficient calculated the reliability of the test scores at 0.834 in the pilot group and 0.889 in the final group. A 3-factor factorial design explains the 62.08% variance. The KMO (Kaiser-Meyer-Olkin) test (p = 0.904), Bartlett’s test of sphericity (126,115.3; p = 0.000010) and the matrix determinant (0.0020770) verified the appropriateness of the factor analysis. The results show that the DESEA questionnaire is a reliable and valid instrument for evaluating desire and interpersonal stress, both in women and men, in clinical and research contexts. Full article

(This article belongs to the Special Issue Sexuality and Sexual Dysfunctions)

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10 pages, 480 KiB

Open AccessArticle

Apelin Improves Prognostic Value of HFSS (Heart Failure Survival Score) and MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) Scales in Ambulatory Patients with End-Stage Heart Failure

by Wioletta Szczurek, Mariusz Gąsior, Michał Skrzypek and Bożena Szyguła-Jurkiewicz

J. Clin. Med. 2020, 9(7), 2300; https://doi.org/10.3390/jcm9072300 - 20 Jul 2020

Cited by 7 | Viewed by 2349

Abstract

This prospective study aimed to determine the effect of adding apelin to the MAGGIC (Meta-Analysis Global Group In Chronic Heart Failure) and HFSS (Heart Failure Survival Score) scales for predicting one-year mortality in 240 ambulatory patients accepted for heart transplantation (HT) between 2015–2017. [...] Read more.

This prospective study aimed to determine the effect of adding apelin to the MAGGIC (Meta-Analysis Global Group In Chronic Heart Failure) and HFSS (Heart Failure Survival Score) scales for predicting one-year mortality in 240 ambulatory patients accepted for heart transplantation (HT) between 2015–2017. The study also investigated whether the combination of N-terminal pro-brain natriuretic peptide (NT-proBNP) with MAGGIC or HFSS improves the ability of these scales to effectively separate one-year survivors from non-survivors on the HT waiting list. The median age of the patients was 58.0 (51.50.0–64.0) years and 212 (88.3%) of them were male. Within a one year follow-up, 75 (31.2%) patients died. The area under the curves (AUC) for baseline parameters was as follows—0.7350 for HFSS, 0.7230 for MAGGIC, 0.7992 for apelin and 0.7028 for NT-proBNP. The HFSS-apelin score generated excellent power to predict the one-year survival, with the AUC of 0.8633 and a high sensitivity and specificity (80% and 78%, respectively). The predictive accuracy of MAGGIC-apelin score was also excellent (AUC: 0.8523, sensitivity of 75%, specificity of 79%). The addition of NT-proBNP to the HFSS model slightly improved the predictive power of this scale (AUC_{HFFSS-NT-proBNP}: 0.7665, sensitivity 83%, specificity 60%), while it did not affect the prognostic strength of MAGGIC (AUC_{MAGGIC-NT-proBNP}: 0.738, sensitivity 71%, specificity 69%). In conclusion, the addition of apelin to the HFSS and MAGGIC models significantly improved their ability to predict the one-year survival in patients with advanced HF. The MAGGIC-apelin and HFSS-apelin scores provide simple and powerful methods for risk stratification in end-stage HF patients. NT-proBNP slightly improved the prognostic power of HFSS, while it did not affect the predictive power of MAGGIC. Full article

(This article belongs to the Section Cardiology)

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63 pages, 2516 KiB

Open AccessReview

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

by Dorian Parisis, Clara Chivasso, Jason Perret, Muhammad Shahnawaz Soyfoo and Christine Delporte

J. Clin. Med. 2020, 9(7), 2299; https://doi.org/10.3390/jcm9072299 - 20 Jul 2020

Cited by 94 | Viewed by 15914

Abstract

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective [...] Read more.

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3–3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the salivary glands are now known to play an active role in the pathogenesis of the disease. The aetiology of the “autoimmune epithelitis” still remains unknown, but certainly involves genetic, environmental and hormonal factors. Later during the disease evolution, the subsequent chronic activation of B cells can lead to the development of systemic manifestations or non-Hodgkin’s lymphoma. The aim of the present comprehensive review is to provide the current state of knowledge on pSS. The review addresses the clinical manifestations and complications of the disease, the diagnostic workup, the pathogenic mechanisms and the therapeutic approaches. Full article

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

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12 pages, 807 KiB

Open AccessArticle

Identification of Prognostic Markers in Patients with Primary Vitreoretinal Lymphoma by Clustering Analysis Using Clinical Data

by Kinya Tsubota, Yoshihiko Usui and Hiroshi Goto

J. Clin. Med. 2020, 9(7), 2298; https://doi.org/10.3390/jcm9072298 - 20 Jul 2020

Cited by 8 | Viewed by 2325

Abstract

(1) Purpose: Primary vitreoretinal lymphoma (PVRL) is associated with poor prognosis because most of the patients with PVRL develop central nerve system lymphoma. The prognostic biomarker of PVRL is largely unknown. Cluster analysis has been used to identify phenotypic groups within various diseases. [...] Read more.

(1) Purpose: Primary vitreoretinal lymphoma (PVRL) is associated with poor prognosis because most of the patients with PVRL develop central nerve system lymphoma. The prognostic biomarker of PVRL is largely unknown. Cluster analysis has been used to identify phenotypic groups within various diseases. In this study, we aimed to describe clinical features of patients with PVRL grouped by clustering analysis and to identify biomarkers for predicting survival prognosis in patients with PVRL. (2) Materials and Methods: Forty patients with PVRL were divided into two groups by clustering analysis using clinical data. Clinical features of the two groups were compared. (3) Result: Clustering analysis classified patients into groups A and B. The survival rate during the follow-up period was significantly lower in group B than in group A (p = 0.03). Serum IgG, serum IgA, vitreous IL-10 and vitreous IL-10 to IL-6 ratio were significantly different between groups A and B (p = 0.03, 0.005, 0.008 and 0.03, respectively). Receiver operating characteristic (ROC) curves generated for the four variables indicated that serum IgA was most suitable for the prediction of prognosis. Patients with serum IgA below 184 mg/dL obtained from the ROC curve had a lower three-year survival rate (p = 0.03) and more episodes of recurrence of lymphoma (3.2 times versus 1.8 times, p = 0.02) compared with patients with serum IgA above 184 mg/dL. (4) Conclusion: The survival rate was significantly different in PVRL patients classified into two groups by clustering analysis. Patients with lower serum IgA had more recurrences and poorer survival than patients with higher IgA. Full article

(This article belongs to the Special Issue Diagnosis and Prognosis in Inflammatory Eye Diseases)

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12 pages, 249 KiB

Open AccessCommunication

Consensus on Recommendations for Safe Sexual Activity during the COVID-19 Coronavirus Pandemic

by Francisco Cabello, Froilán Sánchez, Josep M. Farré and Angel L. Montejo

J. Clin. Med. 2020, 9(7), 2297; https://doi.org/10.3390/jcm9072297 - 20 Jul 2020

Cited by 28 | Viewed by 7122

Abstract

Sexual activity offers numerous advantages for physical and mental health but maintains inherent risks in a pandemic situation, such as the current one caused by SARS-CoV-2. A group of experts from the Spanish Association of Sexuality and Mental Health (AESexSAME) has reached a [...] Read more.

Sexual activity offers numerous advantages for physical and mental health but maintains inherent risks in a pandemic situation, such as the current one caused by SARS-CoV-2. A group of experts from the Spanish Association of Sexuality and Mental Health (AESexSAME) has reached a consensus on recommendations to maintain lower-risk sexual activity, depending on one’s clinical and partner situations, based on the current knowledge of SARS-CoV-2. Different situations are included in the recommendations: a sexual partner passing quarantine without any symptoms, a sexual partner that has not passed quarantine, a sexual partner with some suspicious symptoms of COVID-19, a positive sexual partner with COVID-19, a pregnant sexual partner, a health professional partner in contact with COVID-19 patients, and people without a sexual partner. The main recommendations include returning to engaging in safe sex after quarantine is over (28 days based on the duration one can carry SARS-CoV-2, or 33 days for those who are >60 years old) and all parties are asymptomatic. In all other cases (for those under quarantine, those with some clinical symptoms, health professionals in contact with COVID-19 patients, and during pregnancy), abstaining from coital/oral/anal sex, substituting it with masturbatory or virtual sexual activity to provide maximum protection from the contagion, and increasing the benefits inherent to sexual activity are recommended. For persons without a partner, not initiating sexual activity with a sporadic partner is strongly recommended. Full article

(This article belongs to the Special Issue Sexuality and Sexual Dysfunctions)

11 pages, 706 KiB

Open AccessArticle

Potential Risk of Other-Cause Mortality Due to Long-Term Androgen Deprivation Therapy in Elderly Patients with Clinically Localized Prostate Cancer Treated with Radiotherapy—A Confirmation Study

by Hideya Yamazaki, Koji Masui, Gen Suzuki, Norihiro Aibe, Daisuke Shimizu, Takuya Kimoto, Ken Yoshida and Satoaki Nakamura

J. Clin. Med. 2020, 9(7), 2296; https://doi.org/10.3390/jcm9072296 - 20 Jul 2020

Cited by 4 | Viewed by 2460

Abstract

Androgen deprivation therapy (ADT) is used to improve overall survival (OS) in prostate cancer treatment; however, we encountered that long-term ADT in elderly patients may be related to high other-cause mortality (OCM). This study aimed to confirm the potential risk associated with long-term [...] Read more.

Androgen deprivation therapy (ADT) is used to improve overall survival (OS) in prostate cancer treatment; however, we encountered that long-term ADT in elderly patients may be related to high other-cause mortality (OCM). This study aimed to confirm the potential risk associated with long-term ADT in elderly patients using a different large cohort. A comparison analysis was conducted between the ≥2- and <2-year ADT groups using open, large data from 1840 patients with clinically localized prostate cancer treated with radiotherapy (1172 treated with high-dose-rate brachytherapy (HDR) + external beam radiotherapy (EBRT) and 668 treated with external beam radiotherapy). The OCM-free survival (OCMFS), overall survival, and prostate cancer-specific survival rates were measured. The 10-year OCMFS rates in patients aged ≥75 years were 94.6% and 86% in the <2- and ≥2-year ADT groups, respectively, but were 96.3% and 93.5% (p = 0.0006) in their younger counterparts. If dividing into HDR and EBRT groups. This inclination was found in brachytherapy group but not in EBRT group. The overall survival rate was also lower in the elderly patients in the ≥2-year ADT group than in the <2-year ADT group; however, the 10-year prostate cancer-specific survival rate was the same in both groups. Long-term ADT in elderly patients resulted in not only higher OCM rates but also poorer OS rates; therefore, longer-term ADT in elderly patients should be performed with meticulous care. Full article

(This article belongs to the Section Oncology)

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11 pages, 887 KiB

Open AccessArticle

Major Bleeding Predictors in Patients with Left Atrial Appendage Closure: The Iberian Registry II

by José Ramón López-Mínguez, Juan Manuel Nogales-Asensio, Eduardo Infante De Oliveira, Lino Santos, Rafael Ruiz-Salmerón, Dabit Arzamendi-Aizpurua, Marco Costa, Hipólito Gutiérrez-García, Jose Antonio Fernández-Díaz, Xavier Freixa, Ignacio Cruz-González, Raúl Moreno, Andrés Íñiguez-Romo and Fernando Alfonso-Manterola

J. Clin. Med. 2020, 9(7), 2295; https://doi.org/10.3390/jcm9072295 - 19 Jul 2020

Cited by 11 | Viewed by 2669

Abstract

Introduction and objective: Major bleeding events in patients undergoing left atrial appendage closure (LAAC) range from 2.2 to 10.3 per 100 patient-years in different series. This study aimed to clarify the bleeding predictive factors that could influence these differences. Methods: LAAC was performed [...] Read more.

Introduction and objective: Major bleeding events in patients undergoing left atrial appendage closure (LAAC) range from 2.2 to 10.3 per 100 patient-years in different series. This study aimed to clarify the bleeding predictive factors that could influence these differences. Methods: LAAC was performed in 598 patients from the Iberian Registry II (1093 patient-years; median, 75.4 years). We conducted a multivariate analysis to identify predictive risk factors for major bleeding events. The occurrence of thromboembolic and bleeding events was compared to rates expected from CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, stroke history, vascular disease, sex) and HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, drugs or alcohol) scores. Results: Cox regression analysis revealed that age ≥75 years (HR: 2.5; 95% CI: 1.3 to 4.8; p = 0.004) and a history of gastrointestinal bleeding (GIB) (HR: 2.1; 95% CI: 1.1 to 3.9; p = 0.020) were two factors independently associated with major bleeding during follow-up. Patients aged <75 or ≥75 years had median CHA2DS2-VASc scores of 4 (IQR: 2) and 5 (IQR: 2), respectively (p < 0.001) and HAS-BLED scores were 3 (IQR: 1) and 3 (IQR: 1) for each group (p = 0.007). Events presented as follow-up adjusted rates according to age groups were stroke (1.2% vs. 2.9%; HR: 2.4, p = 0.12) and major bleeding (3.7 vs. 9.0 per 100 patient-years; HR: 2.4, p = 0.002). Expected major bleedings according to HAS-BLED scores were 6.2% vs. 6.6%, respectively. In patients with GIB history, major bleeding events were 6.1% patient-years (HAS-BLED score was 3.8 ± 1.1) compared to 2.7% patients-year in patients with no previous GIB history (HAS-BLED score was 3.4 ± 1.2; p = 0.029). Conclusions: In this high-risk population, GIB history and age ≥75 years are the main predictors of major bleeding events after LAAC, especially during the first year. Age seems to have a greater influence on major bleeding events than on thromboembolic risk in these patients. Full article

(This article belongs to the Special Issue New Perspective in Atrial Fibrillation)

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14 pages, 806 KiB

Open AccessArticle

Sociodemographic Inequalities in Outcomes of a Swedish Nationwide Self-Management Program for Osteoarthritis: Results from 22,741 Patients between Years 2008–2017

by Erik Unevik, Allan Abbott, Stefan Fors and Ola Rolfson

J. Clin. Med. 2020, 9(7), 2294; https://doi.org/10.3390/jcm9072294 - 19 Jul 2020

Cited by 5 | Viewed by 2951

Abstract

The aim of this study is to investigate if there are educational level and birthplace related differences in joint-related pain, health-related quality of life (HRQoL), willingness to undergo joint surgery, walking difficulties, physical activity level, fear-avoidance behavior before, as well as three and [...] Read more.

The aim of this study is to investigate if there are educational level and birthplace related differences in joint-related pain, health-related quality of life (HRQoL), willingness to undergo joint surgery, walking difficulties, physical activity level, fear-avoidance behavior before, as well as three and 12 months after participation in a structured self-management program for hip and knee osteoarthritis. Differences in adherence to and use of knowledge from the program were also investigated. An observational national register-based study was performed with a prospective longitudinal design using patient and physiotherapist-reported data on 22,741 complete cases from the National Quality Register for better management of patients with osteoarthritis (BOA) during years 2008–2017. At baseline and after three and 12 months follow-up, higher educational level and being domestic-born was associated with less joint-related pain, better HRQoL, lower willingness to undergo joint surgery, fewer walking difficulties, higher physical activity level, and less fear-avoidance behavior. Foreign born individuals demonstrated higher adherence to exercise and reported better use of the self-management program. The BOA self-management program may require further pedagogical refinement to suit participants of different sociodemographic backgrounds and health literacy. A more patient-centered delivery, sensitive to educational, ethnic, and cultural differences may potentially reduce inequalities in future outcomes. Full article

(This article belongs to the Special Issue Orthopaedic Diseases and Rehabilitation)

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16 pages, 5381 KiB

Open AccessArticle

Bone Morphogenetic Protein (BMP)4 But Not BMP2 Disrupts the Barrier Integrity of Retinal Pigment Epithelia and Induces Their Migration: A Potential Role in Neovascular Age-Related Macular Degeneration

by Ahmed S. Ibrahim, Khaled Hussein, Fang Wang, Ming Wan, Nancy Saad, Maamon Essa, Ivana Kim, Akbar Shakoor, Leah A. Owen, Margaret M. DeAngelis and Mohamed Al-Shabrawey

J. Clin. Med. 2020, 9(7), 2293; https://doi.org/10.3390/jcm9072293 - 19 Jul 2020

Cited by 11 | Viewed by 4133

Abstract

Disruption of retinal pigment epithelial (RPE) barrier integrity and RPE migration are hallmark features in neovascular age-related macular degeneration (nAMD), but the underlying causes and pathophysiology are not completely well-defined. Herein, we aimed to evaluate the effect of bone morphogenetic proteins (BMPs) on [...] Read more.

Disruption of retinal pigment epithelial (RPE) barrier integrity and RPE migration are hallmark features in neovascular age-related macular degeneration (nAMD), but the underlying causes and pathophysiology are not completely well-defined. Herein, we aimed to evaluate the effect of bone morphogenetic proteins (BMPs) on the barrier function and migration of RPE. In particular, we investigated the role of BMP2 and BMP4 in these processes as our analysis of RNA-sequencing (seq) data from human donor eyes demonstrated that they are highly differentially expressed BMP members in macular RPE/choroid versus macular retina. We used electrical cell-substrate impedance sensing (ECIS) system to monitor precisely in real time the barrier integrity and migration of ARPE-19 after treatment with various concentrations of BMP2 or BMP4. Immunofluorescence was also used to assess the changes in the expression and the organization of the key tight junction protein, zona occludens (ZO)-1, in ARPE-19 cells under BMP2 or BMP4 treatment. This was followed by measuring the activity of matrix metalloproteinases (MMPs). Finally, RNA-seq and ELISA were used to determine the local and circulating levels of BMP2 and BMP4 in retinas and serum samples from nAMD donors. Our ECIS results showed that BMP4 but not BMP2 decreased the transcellular electrical resistance (TER) of ARPE-19 and increased their migration in comparison with control (vehicle-treated cells). Furthermore, immunofluorescence showed a disorganization of ZO-1 in BMP4-treated ARPE-19 not in BMP2-treated cells or vehicle-treated controls. This effect of BMP4 was associated with significant increases in the activity of MMPs, specifically MMP2. Lastly, these results were corroborated by additional findings that circulating but not local BMP4 levels were significantly higher in nAMD donor samples compared to controls. Collectively, our results demonstrated unreported effects of BMP4 on inducing RPE dysfunction and suggest that BMP4 but not BMP2 may represent a potential therapeutic target in nAMD. Full article

(This article belongs to the Special Issue Prevention and Treatments of Age-Related Macular Degeneration)

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13 pages, 2196 KiB

Open AccessArticle

Exercise Training Protects against Atorvastatin-Induced Skeletal Muscle Dysfunction and Mitochondrial Dysfunction in the Skeletal Muscle of Rats

by Dae Yun Seo, Jun-Won Heo, Mi-Hyun No, Su-Zi Yoo, Jeong Rim Ko, Dong-Ho Park, Ju-Hee Kang, Chang-Ju Kim, Su-Jeen Jung, Jin Han and Hyo-Bum Kwak

J. Clin. Med. 2020, 9(7), 2292; https://doi.org/10.3390/jcm9072292 - 19 Jul 2020

Cited by 7 | Viewed by 3739

Abstract

Statins are used to prevent and treat atherosclerotic cardiovascular disease, but they also induce myopathy and mitochondrial dysfunction. Here, we investigated whether exercise training prevents glucose intolerance, muscle impairment, and mitochondrial dysfunction in the skeletal muscles of Wistar rats treated with atorvastatin (5 [...] Read more.

Statins are used to prevent and treat atherosclerotic cardiovascular disease, but they also induce myopathy and mitochondrial dysfunction. Here, we investigated whether exercise training prevents glucose intolerance, muscle impairment, and mitochondrial dysfunction in the skeletal muscles of Wistar rats treated with atorvastatin (5 mg kg⁻¹ day⁻¹) for 12 weeks. The rats were assigned to the following three groups: the control (CON), atorvastatin-treated (ATO), and ATO plus aerobic exercise training groups (ATO+EXE). The ATO+EXE group exhibited higher glucose tolerance and forelimb strength and lower creatine kinase levels than the other groups. Mitochondrial respiratory and Ca²⁺ retention capacity was significantly lower in the ATO group than in the other groups, but exercise training protected against atorvastatin-induced impairment in both the soleus and white gastrocnemius muscles. The mitochondrial H₂O₂ emission rate was relatively higher in the ATO group and lower in the ATO+EXE group, in both the soleus and white gastrocnemius muscles, than in the CON group. In the soleus muscle, the Bcl-2, SOD1, SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. In the white gastrocnemius muscle, the SOD2, Akt, and AMPK phosphorylation levels were significantly higher in the ATO+EXE group than in the ATO group. Therefore, exercise training might regulate atorvastatin-induced muscle damage, muscle fatigue, and mitochondrial dysfunction in the skeletal muscles. Full article

(This article belongs to the Special Issue Advances in Metabolic Myopathies)

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10 pages, 1141 KiB

Open AccessArticle

Mother-to-Infant Bonding in Women with Postpartum Psychosis and Severe Postpartum Depression: A Clinical Cohort Study

by Janneke Gilden, Nina M. Molenaar, Anne K. Smit, Witte J. G. Hoogendijk, Anna-Sophie Rommel, Astrid M. Kamperman and Veerle Bergink

J. Clin. Med. 2020, 9(7), 2291; https://doi.org/10.3390/jcm9072291 - 19 Jul 2020

Cited by 36 | Viewed by 8288

Abstract

Mother-to-infant bonding is important for long-term child development. The aim of this study was to investigate bonding in women admitted to a Mother and Baby Unit with postpartum depression (PD, n = 64) and postpartum psychosis (PP, n = 91). Participants completed the [...] Read more.

Mother-to-infant bonding is important for long-term child development. The aim of this study was to investigate bonding in women admitted to a Mother and Baby Unit with postpartum depression (PD, n = 64) and postpartum psychosis (PP, n = 91). Participants completed the Postpartum Bonding Questionnaire (PBQ), the Edinburgh Postnatal Depression Scale (EPDS) and the Young Mania Rating Scale (YMRS) weekly during admission. At admission, 57.1% of women with PD had impaired bonding, compared to only 17.6% of women with PP (p-value < 0.001). At discharge, only 18.2% of women with PD and 5.9% of women with PP still experienced impaired bonding (p-value = 0.02). There was a strong association between decrease of depressive and manic symptoms and improved bonding over an eight-week admission period. In a small group of women (5.7%) impaired bonding persisted despite being in remission of their psychiatric disorder. The results from our study show that impaired bonding is a more present and evidently severe problem in postpartum depression but not so much in postpartum psychosis. Treatment of depressive symptoms will improve bonding in almost all women, but clinicians should assess if impaired bonding is still present after remission because for a small group special care and treatment focused on bonding might be required. Full article

(This article belongs to the Special Issue Pregnancy and Bipolar Disorder)

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J. Clin. Med., Volume 9, Issue 7 (July 2020) – 303 articles

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